title: Risk of geographic atrophy in the comparison of age-related macular degeneration treatments trials.
abstract: OBJECTIVE
  To describe risk factors for geographic atrophy (GA) in the Comparison of Age-related Macular Degeneration Treatments Trials (CATT).
  
  
  METHODS
  Cohort within a randomized clinical trial.
  
  
  METHODS
  We analyzed 1024 CATT patients with no GA visible on color fundus photographs (CFPs) and/or fluorescein angiograms (FAs) at enrollment.
  
  
  METHODS
  Eyes were assigned to ranibizumab (0.5 mg) or bevacizumab (1.25 mg) treatment and to a 2-year monthly or pro re nata (PRN) injection regimen, or monthly injections for 1 year and PRN for 1 year. Demographic, genetic, and baseline ocular characteristics and lesion features of CFP/FA and optical coherence tomography (OCT) were evaluated as risk factors for GA through 2 years of follow-up. Time-dependent Cox proportional hazard models were used to estimate adjusted hazard ratios (aHRs).
  
  
  METHODS
  Development of GA.
  
  
  RESULTS
  By 2 years, GA developed in 187 of 1024 patients (18.3%). Baseline risk factors for GA development included baseline visual acuity (VA) ≤20/200 (aHR, 2.65; 95% confidence interval [CI], 1.43-4.93), retinal angiomatous proliferation (RAP; aHR, 1.69; 95% CI, 1.16-2.47), GA in the fellow eye (aHR, 2.07; 95% CI, 1.40-3.08), and intraretinal fluid at the foveal center (aHR, 2.10; 95% CI, 1.34-3.31). Baseline factors associated with lower risk for GA development included blocked fluorescence (aHR, 0.49; 95% CI, 0.29-0.82), OCT measurements of subretinal fluid thickness of >25 μ (aHR, 0.52; 95% CI, 0.35-0.78), subretinal tissue complex thickness of >275 compared with ≤75 μ (aHR, 0.31; 95% CI, 0.19-0.50), and vitreomacular attachment (aHR, 0.55; 95% CI, 0.31-0.97). Ranibizumab compared with bevacizumab had a higher risk (aHR, 1.43; 95% CI, 1.06-1.93), and monthly dosing had a higher risk (aHR, 1.59; 95% CI, 1.17-2.16) than PRN dosing. There were no strong associations between development of GA and the presence of risk alleles for CFH, ARMS 2, HTRA1, C3, or TLR3.
  
  
  CONCLUSIONS
  Approximately one fifth of CATT patients developed GA within 2 years of treatment. Independent baseline risk factors included poor VA, RAP, foveal intraretinal fluid, monthly dosing, and treatment with ranibizumab. Anti-vascular endothelial growth factor therapy may have a role in the development of GA.
authors.affiliation: Department of Ophthalmology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania. Electronic address: juangrun@mail.med.upenn.edu.
authors.forename: Juan E
authors.initials: JE
authors.lastname: Grunwald
authors.affiliation: Department of Ophthalmology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Ebenezer
authors.initials: E
authors.lastname: Daniel
authors.affiliation: Department of Ophthalmology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Jiayan
authors.initials: J
authors.lastname: Huang
authors.affiliation: Department of Ophthalmology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Gui-Shuang
authors.initials: GS
authors.lastname: Ying
authors.affiliation: Department of Ophthalmology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Maureen G
authors.initials: MG
authors.lastname: Maguire
authors.affiliation: Department of Ophthalmology, Duke University, Durham, North Carolina; Department of Biomedical Engineering, Duke University, Durham, North Carolina.
authors.forename: Cynthia A
authors.initials: CA
authors.lastname: Toth
authors.affiliation: Department of Ophthalmology, Duke University, Durham, North Carolina; Duke Reading Center, Duke University Eye Center, Durham, North Carolina.
authors.forename: Glenn J
authors.initials: GJ
authors.lastname: Jaffe
authors.affiliation: Department of Ophthalmology, University of Colorado-Denver, Aurora, Colorado.
authors.forename: Stuart L
authors.initials: SL
authors.lastname: Fine
authors.affiliation: Department of Ophthalmology, University of Wisconsin, Madison, Wisconsin.
authors.forename: Barbara
authors.initials: B
authors.lastname: Blodi
authors.affiliation: Casey Eye Institute, Oregon Health Sciences University, Portland, Oregon.
authors.forename: Michael L
authors.initials: ML
authors.lastname: Klein
authors.affiliation: Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio.
authors.forename: Alison A
authors.initials: AA
authors.lastname: Martin
authors.affiliation: Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio.
authors.forename: Stephanie A
authors.initials: SA
authors.lastname: Hagstrom
authors.affiliation: Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio.
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Martin
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D000068258:Bevacizumab; D015331:Cohort Studies; D005260:Female; D005451:Fluorescein Angiography; D005500:Follow-Up Studies; D060005:Genotyping Techniques; D057092:Geographic Atrophy / Q000175:diagnosis / Q000188:drug therapy / Q000453:epidemiology*; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D000069579:Ranibizumab; D012307:Risk Factors; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors; D014792:Visual Acuity / Q000502:physiology; D057135:Wet Macular Degeneration / Q000175:diagnosis / Q000188:drug therapy / Q000453:epidemiology*
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab; D000069579:Ranibizumab